title: In search of CML stem cells' deadly weakness.
abstract: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder that is characterized by the presence of a fusion oncogene, BCR-ABL, which encodes a protein with constitutive tyrosine kinase activity. This activity causes excessive production of myeloid cells and their premature release into the circulation. The discovery of tyrosine kinase inhibitors marked a major advance in CML therapy, but these drugs cannot eradicate the disease because they are unable to kill the most primitive, quiescent leukemic stem cells. This review discusses current research in CML and attractive targets that have emerged with potential for eradicating the disease. Several new targets have recently been investigated as potential modulators in myeloid leukemia pathogenesis, including the multiple gene regulators miRNAs, the apparently leukemia-specific cell surface marker IL1RAP, transcription factors such as BMI1 and FOXOs, the tumor suppressors PML and PP2A, and the tyrosine kinase JAK2.
authors.affiliation: Paul O'Gorman Leukaemia Research Centre, Institute for Cancer Sciences, University of Glasgow, 21 Shelley Road, G12 0ZD Glasgow, UK. francesca.pellicano@glasgow.ac.uk
authors.forename: Francesca
authors.initials: F
authors.lastname: Pellicano
authors.forename: Amy
authors.initials: A
authors.lastname: Sinclair
authors.forename: Tessa L
authors.initials: TL
authors.lastname: Holyoake
mesh_terms: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D053577:Interleukin-1 Receptor Accessory Protein / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics; D063150:Polycomb Repressive Complex 1; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics
chemical_list: C069077:BMI1 protein, human; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C507765:IL1RAP protein, human; D053577:Interleukin-1 Receptor Accessory Protein; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; D016044:Fusion Proteins, bcr-abl